SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

OBJECTIVE: To carry out amniocyte karyotyping analysis and chromosomal microarray analysis (CMA) for women with anomalies revealed by fetal echocardiography. METHODS: From January 2019 to December 2021, genetic testing was carried out for 205 fetuses including 97 with soft marker anomalies and 108 with structural heart abnormalities. Among these, 138 only had abnormal fetal echocardiography, whilst 38 and 29 were complicated with extracardiac soft marker anomalies and extracardiac structural malformation, respectively. RESULTS: No significant difference was detected in the detection rate of genetic anomalies between fetuses with heart-related soft markers and those with abnormal heart structures (P > 0.05). Compared with those with abnormal fetal echocardiography alone, the detection rates of chromosomal aneuploidies in those with abnormal extracardiac soft markers or abnormal extracardiac structures were significantly higher (P < 0.05). Twenty-eight chromosomal aneuploidies (including a rare mosaicism), 2 balanced translocations and 1 supernumerary marker chromosome were detected by karyotyping analysis. Twenty-seven aneuploidies, 19 copy number variations (CNVs) and 1 uniparental disomy were detected by CMA. CONCLUSION Prenatal diagnosis has attached great importance to the suggestive role of fetal heart-related soft markers, and chromosomal aneuploidies are more common among fetuses with abnormal extracardiac soft markers and extracardiac structural abnormalities. Chromosomal Karyotyping is useful for the detection of balanced translocations and mosaicisms. CMA is helpful for the detection of CNVs. Identification of the genetic causes can facilitate genetic counseling for the affected couples.
Pregnancy ; Female ; Humans ; DNA Copy Number Variations ; Prenatal Diagnosis ; Fetus ; Echocardiography ; Aneuploidy ; Mosaicism ; Translocation, Genetic

Objective:To explore the clinical significance of different metabolic parameters measured by 18F-fluorodeoxyglucose (FDG) PET/CT in predicting the effectiveness of chemotherapy in advanced lung adenocarcinoma patients. Methods:A set of metabolic parameters of PET/CT and clinical characteristics which were detected from 127 patients (70 males, 57 females, age (56.8±10.1) years) with advanced lung adenocarcinoma treated with at least two cycles of chemotherapy in Hainan Cancer Hospital between August 2017 and June 2019 were retrospectively analyzed. The effects of those parameters on patients′ survival were analyzed by receiver operating characteristic (ROC) curve, Kaplan-Meier method (log-rank test) and Cox proportional hazards model.Results:Maximum standardized uptake value (SUV max), metabolic tumor volume 30% (MTV 30), and total lesion glycolysis 30% (TLG 30) had larger areas under the curve (0.581, 0.606 and 0.693 respectively) compared with other imaging parameters, and the optimal cut-off values were 10.12, 20.21 cm 3 and 81.25 g respectively. Kaplan-Meier univariate and Cox analyses synergistically showed that clinical stage (hazard ratio ( HR)=0.293(95% CI: 0.190-0.451), P<0.001), smoking ( HR=0.732(95% CI: 0.605-0.885), P=0.001), and MTV 30 ( HR=1.555(95% CI: 1.078-2.242), P=0.018) had significant predictive value for progression-free survival (PFS). Stratified analysis showed that smoking and MTV 30>20.21 cm 3 were independent prognostic factors for poor PFS in patients with advanced lung adenocarcinoma receiving chemotherapy ( HR=0.738(95% CI: 0.611-0.893), P=0.002; HR=1.502(95% CI: 1.037-2.177), P=0.032). Conclusions:Clinical stage, smoking and MTV 30 are independent prognostic factors of PFS in patients with advanced lung adenocarcinoma receiving chemotherapy. MTV 30≤20.21 cm 3 is expected to be an image biomarker for predicting survival and selecting patients with advanced lung adenocarcinoma who are more likely to benefit from chemotherapy.

Objective: To investigate the influence of five-in-one management mode(standardized asthma treatment, asthma diary, peak expiratory flow (PEF) monitoring, reasonable diet and physical exercise) on disease prevention and control of school children with asthma. Methods: From April to October 2018, 70 children with asthma in clinical remission were selected from Affiliated Hospital of Qingdao University using randomized controlled study design. These children were randomly divided into study group and control group, with 35 cases in each group. In the study group, 5 cases were lost to follow-up, and 30 cases were actually enrolled. In the control group, 6 cases were lost to follow-up, and 29 cases were actually enrolled. Children in the control group received routine medication and regular outpatient consultation, and children in the study group received the five-in-one asthma management model. In the first time of seeing a doctor, after 3 months and 6 months of follow-up, asthma control test score, medication compliance index score and lung function index (forced expiratory volume in 1 second (FEV1), PEF were evaluated respectively.Parental satisfaction, asthma acute episodes, weight, height and biochemical index were recorded during the 6 months of follow-up. Pulmonary function index, asthma control score and body mass index of overweight children with asthma were compared with t-test, medication compliance was compared with chi-square test, and the rank sum test was used for the comparison of the number of emergency visits of asthma attacks and parents′ satisfaction. Results: A total of 59 children with asthma were included, among them 30 were in the study group (8.1±1.5) years old and 29 in the control group (9.2±1.1) years old. After 3 months of follow-up, FEV1, PEF, asthma control score in the study group were (86.3±1.5)%, (83.3±2.4)%, (24.7±2.6) points respectively; and in the control group, FEV1, PEF, asthma control score were (84.4±2.5)%, (82.2±1.9)%, (21.1±1.3) points respectively. The indicators in the study group were higher than those in the control group (t=3.62, 1.97, 6.64, P<0.05). After 6 months of follow-up, FEV1, PEF, asthma control score in the study group were (88.4±2.3)%, (85.4±2.2)%, (26.8±1.8) points respectively; and in the control group, FEV1, PEF, asthma control score were (85.5±1.9)%, (83.2±1.7)%, (22.5±1.4) points respectively. The indicators in the study group were significantly higher than those in the control group (t=5.34, 4.24, 10.41, P<0.05). During the 6-month follow up, the number of emergency visits of asthma attacks in the study group and in the control group were 0.42(0.36, 0.51) and 0.92(0.72, 1.27) respectively. The indicator in the study group was significantly lower than that in the control group (Z=3.21, P<0.05). After 3 months of follow-up, the proportions of children with good compliance in the study group and control group were 67% (20/30) and 62% (18/29), the proportions of poor compliance were 27% (8/30) and 34% (10/29), the proportions of non-compliance were 7% (2/30) and 7% (2/29). There were no statistically significant differences (χ²=0.14, 0.43, 0.00, P=0.71, 0.51, 0.97). After 6 months of follow-up, the proportions of children with good compliance in the study group and control group were 87% (26/30) and 69% (20/29), the proportion of poor compliance were 10% (3/30) and 28% (8/29), the proportion of non-compliance were 3% (1/30) and 7% (2/29), There were no statistically significant differences (χ²=2.70, 3.00, 0.39, P=0.10, 0.08, 0.53). After 6 months of follow-up, the number of great satisfaction, satisfaction and dissatisfaction in the study group were 20, 10 and 0 respectively, the satisfaction rate was 100%, meanwhile those indicators in the control group were 4, 15 and 10 respectively, the satisfaction rate was 66%, The indicator in the study group was significantly higher than that in the control group (Z=4.60, P<0.05). Conclusions The application of "five-in-one" asthma management model (standardized asthma treatment, asthma diary, PEF monitoring, reasonable diet and physical exercise) for school-age children with asthma can significantly improve lung function, as well as reduce the number of acute asthma attacks. It has a high parent satisfaction, therefore it should be recommended for clinical implementation.

Objective: To investigate the expression and clinical significance of PD-1 molecule in tumor cells (T-ALL cells) derived from the patient with T-cell acute lymphoblastic leukemia (T-ALL). Methods: T-ALL cells from one patient and PBMCs from four healthy volunteers provided by the Department of Hematology in Jiangsu Provincial Hospital of Traditional Chinese Medicine in December 2015, and human 293T/PD-1 cells provided by Persongen Bio Therapeutics (Suzhou) Co., Ltd. were used for this study. The mouse T-ALL xenograft model was constructed by injecting T-ALL cells into tail vein of B-NDG mice, and flow cytometry was used to verify whether the cells obtained from the spleen of transplanted mice were mainly consisted of T-ALL cells. Flow cytometry was used to study the protein expression of PD-1 in T-ALL cells, and RT-PCR was applied to further verify the mRNA expression of PD-1 in T-ALL cells. The PD-1 gene in T-ALL cells was sequenced by SNP genotyping to detect whether the DNA sequence of PD-1 gene changed. PD-1 inhibitor was used in vitro to study their effects on proliferation, apoptosis, and the mRNA expression levels of related factors in T-ALL cells. Results: The mouse T-ALL xenograft model was successfully constructed and verified by flow cytometry as T-ALL. PD-1 was highly expressed at both mRNA and protein levels in T-ALL cells (all P<0.01). A C-to-T mutation was detected in the fifth exon of the PD-1 gene. PD-1 inhibitor had no significant effect on proliferation and apoptosis of T-ALL cells in vitro; PD-1 inhibitor up-regulated the mRNA expression of tumor-suppressor protein IGFBP3 and decreased the mRNA expression of oncoprotein SULT1A3 (all P<0.01). Conclusion: PD-1 is highly expressed in T-ALL cells, and PD-1 could be used as a target for clinical diagnosis and treatment for T-ALL.

To investigate the influence of five?in?one management mode (standardized asthma treatment, asthma diary, peak expiratory flow (PEF) monitoring, reasonable diet and physical exercise) on disease prevention and control of school children with asthma. Methods From April to October 2018, 70 children with asthma in clinical remission were selected from Affiliated Hospital of Qingdao University using randomized controlled study design. These children were randomly divided into study group and control group, with 35 cases in each group. In the study group, 5 cases were lost to follow?up, and 30 cases were actually enrolled. In the control group, 6 cases were lost to follow?up, and 29 cases were actually enrolled. Children in the control group received routine medication and regular outpatient consultation, and children in the study group received the five?in?one asthma management model. In the first time of seeing a doctor, after 3 months and 6 months of follow?up, asthma control test score, medication compliance index score and lung function index (forced expiratory volume in 1 second (FEV1), PEF were evaluated respectively. Parental satisfaction, asthma acute episodes, weight, height and biochemical index were recorded during the 6 months of follow?up. Pulmonary function index, asthma control score and body mass index of overweight children with asthma were compared with t-test, medication compliance was compared with chi?square test, and the rank sum test was used for the comparison of the number of emergency visits of asthma attacks and parents'satisfaction. Results A total of 59 children with asthma were included, among them 30 were in the study group (8.1 ± 1.5) years old and 29 in the control group (9.2±1.1) years old. After 3 months of follow?up, FEV1, PEF, asthma control score in the study group were (86.3 ± 1.5)% , (83.3 ± 2.4)% , (24.7 ± 2.6) points respectively; and in the control group, FEV1, PEF, asthma control score were (84.4±2.5)%, (82.2±1.9)%, (21.1±1.3) points respectively. The indicators in the study group were higher than those in the control group (t=3.62, 1.97, 6.64, P<0.05). After 6 months of follow?up, FEV1, PEF, asthma control score in the study group were (88.4±2.3)%, (85.4±2.2)%, (26.8±1.8) points respectively; and in the control group, FEV1, PEF, asthma control score were (85.5±1.9)%, (83.2± 1.7)%, (22.5±1.4) points respectively. The indicators in the study group were significantly higher than those in the control group (t=5.34, 4.24, 10.41, P<0.05). During the 6?month follow up, the number of emergency visits of asthma attacks in the study group and in the control group were 0.42(0.36, 0.51) and 0.92(0.72, 1.27) respectively. The indicator in the study group was significantly lower than that in the control group (Z=3.21, P<0.05). After 3 months of follow?up, the proportions of children with good compliance in the study group and control group were 67% (20/30) and 62% (18/29), the proportions of poor compliance were 27% (8/30) and 34% (10/29), the proportions of non?compliance were 7% (2/30) and 7% (2/29). There were no statistically significant differences (χ2=0.14, 0.43, 0.00, P=0.71, 0.51, 0.97). After 6 months of follow?up, the proportions of children with good compliance in the study group and control group were 87% (26/30) and 69% (20/29), the proportion of poor compliance were 10% (3/30) and 28% (8/29), the proportion of non?compliance were 3% (1/30) and 7% (2/29), There were no statistically significant differences (χ2=2.70, 3.00, 0.39, P=0.10, 0.08, 0.53). After 6 months of follow?up, the number of great satisfaction, satisfaction and dissatisfaction in the study group were 20, 10 and 0 respectively, the satisfaction rate was 100%, meanwhile those indicators in the control group were 4, 15 and 10 respectively, the satisfaction rate was 66%, The indicator in the study group was significantly higher than that in the control group (Z=4.60, P<0.05). Conclusions The application of "five?in?one" asthma management model (standardized asthma treatment, asthma diary, PEF monitoring, reasonable diet and physical exercise) for school?age children with asthma can significantly improve lung function, as well as reduce the number of acute asthma attacks. It has a high parent satisfaction, therefore it should be recommended for clinical implementation.

Through checking the ancient books and the articles at the modern times and combining the disciplinary characteristics of techniques of acupuncture and moxibustion, the training of manipulation skills was discussed. It is proposed that during the teaching of the techniques of acupuncture and moxibustion, the most basic ability of needling technique should be trained in the first place. This ability includes the ability of spiritual cultivation, the ability of tactile perception and the specific training for the needling techniques. The ability of spiritual cultivation refers to the consciousness concentration to the patient when providing acupuncture, which may promotes and conducts to the affected area. The ability of tactile perception refers to the different feelings of different tissues under the hands before and after acupuncture, the perception to the different needling sensations corresponding to the chief complains of patients as well as the different body responses after acupuncture. In order to ensure the better learning results, the specific manipulations of needling techniques should be provided accordingly on the base of these basic training skills of acupuncture.
Acupuncture ; education ; Books ; Learning ; Moxibustion ; Teaching

ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8％.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95％CI:0.987-1.570,P=0.065),male gender(OR:0.433,95％CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95％CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95％CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95％CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.

Objective To describe the distribution of medication costs of rheumatoid arthritis patients, and to analyze the factors that may affect the costs. Methods Data were obtained from a 12-month retrospective investigation of patients with rheumatoid arthritis (RA) across China. Department of Rheuma-tology of 18 hospitals were randomly selected. The data about their social conditions, clinical conditions, medications associated with RA such as disease-modifying antirheumatic drugs (DMARDs), non -steroidal anti -inflammtory drugs (NSAIDs), steroids, biologic agents were collected, and the costs of drugs were calculated. A non-parameter test and multivariate logistic regression analysis were performed. Results Six hundred and forty six patients were enrolled into the study, 435 completed data were chosen for analysis. The results demonstrated that the average costs per patient for medications in the past year was 8018 . The total medication costs were further subdivided into the following parts: DMARDs, (represented 20% of the total costs), biologic drugs (49%), NSAIDs (4%), herbal drugs (22%), steroids (1%). Data analysis showed that patients with higher education and higher incomes, with medical insurance,better health function status and outpatients paid more on DMARDs. Extra-articular manifestations increased the odds of the high-cost group (OR: 2.180, 95%CI: 1.335～3.558, P=0.002), while poor health function status increased the probability of paying high costs (OR: 1.373, 95%CI: 1.012～1.863, P=0.041). Conclusion High medication costs in RA do exist in RA patients. The costs of medication is associated with health function status and the presence of extra-articular manifestations.

Objective To investigate the character of real-time gray-scale contrast-enhanced ultrasonography (CEUS) and its clinical value in diagnosing hepatic focal lesion. Methods One hundred and three patients with 142 focal hepatic lesions were examined by CEUS after an intravenous administration of the contrast agent, then the characters of the images were analyzed. Results The initial contrast-enhanced signal patterns were classified into 5 modes, peak contrast-enhanced signal patterns into 4 modes, and contrast agent perfusion patterns into 7 modes. Different lesions had different characters of contrast-enhanced phases. The accuracy rate of the CEUS in diagnosing focal hepatic lesion was 93.0%. which was significantly higher than that of conventional ultrasound and contrast-enhanced CT (X2=47.430, P<0.05). Conclusions The characteristic initial contrast-enhanced pattern and contrast agent perfusion pattern are helpful in the differential diagnosis of hepatic focal lesion, while peak contrast-enhanced signal pattern is relatively unreliable. Compared with conventional ultrasound and contrast-enhanced CT, CEUS can dramatically improve the accuracy of qualitative diagnosis of hepatic focal lesion.